Cell therapy for nonischemic dilated cardiomyopathy: A systematic review and meta-analysis of randomized controlled trials.

Cell therapy involves transplantation of human cells to promote repair of diseased or injured tissues and/or cells. Only a limited number of mostly small-scale trials have studied cell therapy in nonischemic cardiomyopathy (NICM). We performed a meta-analysis of randomized clinical trials (RCTs) to assess the safety and efficacy of cell therapy in NICM. Electronic databases were searched for relevant RCTs from inception until August 2020. Outcomes assessed were left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter or volume (LVEDD), quality of life (QoL) indices, and major adverse cardiac events (MACEs). Weighted mean differences (MDs) and standardized mean differences (SMDs) were calculated using random-effects methods. Eleven RCTs with 574 participants were included in the analysis. There was a significant increase in mean LVEF (MD, 4.17%; 95% confidence interval [CI] = 1.66-6.69) and modest decrease in LVEDD (SMD, -0.50; 95% CI = -0.95 to -0.06) in patients treated with cell therapy compared with controls. Cell therapy was also associated with improvement in functional capacity, as assessed by the 6-minute walking distance (MD, 72.49 m; 95% CI = 3.44-141.53). No significant differences were seen in MACEs and QoL indices between treated and control groups. This meta-analysis suggests that cell therapy may improve LV systolic function and may be associated with improvement in LVEDD and functional capacity compared with maximal medical therapy. Cell therapy was safe, with no significant difference in MACEs between treatment and control groups. However, given the limitations of current studies, larger well-designed RCTs are needed to evaluate the efficacy of cell therapy in patients with NICM.

Trends in Incidence and Outcomes of Pregnancy-Related Acute Myocardial Infarction (From a Nationwide Inpatient Sample Database).

Acute myocardial infarction (AMI) during pregnancy is rare but fatal complication. Recent incidence of pregnancy related AMI and trends in the related outcomes are unknown. The Nationwide Inpatient Sample database was utilized from years 2005 to 2014. International Classification of Disease-Ninth Revision were used to identify pregnancy related admissions and AMI. Primary outcome was incidence and trend of AMI related to pregnancy and Secondary outcomes were trends in mortality, resource utilization, and predictors of AMI during pregnancy. Simple logistic regression model was used to calculate predictors of AMI during pregnancy. p Values for trends were generated by Cochrane-Armitage test for categorical variables and simple linear regression for continuous variables. A total of 43,437,621 pregnancy related hospitalization and 3,786 cases of AMI (86% ante-partum and 14% postpartum) were noted during study period. The incidence of AMI during the study period was 8.7 per 100,000 pregnancies with an overall increase in incidence during the study period (relative increase of 18.9%, p <0.001). There was a concomitant decrease in mortality (relative decrease of 40.05%, p <0.001), cost of care (relative decrease of 8.70%, p <0.001), and length of stay (relative decrease of 13.53%, p <0.001). Significant predictors of AMI during pregnancy were higher age of pregnancy, black race, co-morbidities such as hypertension, thrombophilia, diabetes milletus, substance abuse, smoking, hyperlipidemia, heart failure, deep venous thrombosis, transfusion, fluid and electrolyte imbalance, and postpartum complications such as hemorrhage, infection, and depression. In conclusion, the incidence of AMI 2005 to 2014 rose with a concomitant decrease in mortality and resource utilization. High-risk patient characteristics were identified which could be utilized for resource allocation to further improve outcomes.

Drug-Eluting Stents Versus Bare-Metal Stents in Saphenous Vein Graft Intervention.

Background Percutaneous coronary intervention with drug-eluting stents (DES) has been increasingly used for revascularization of saphenous vein graft stenosis without strong clinical evidence favoring their use. Randomized controlled trials comparing DES versus bare-metal stents (BMS) in saphenous vein graft-percutaneous coronary intervention have been inconclusive. Methods and Results We performed a comprehensive literature search through May 15, 2018, for all eligible studies comparing DES versus BMS in patients with saphenous vein graft stenosis in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Clinical outcomes included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, myocardial infarction, stent thrombosis, and target vessel revascularization. Six randomized controlled trials were eligible and included 1582 patients, of whom 797 received DES and 785 received BMS. The follow-up period ranged from 18 months to 60 months. There was no statistically significant difference between DES and BMS for all-cause mortality (risk ratio [RR],1.11; 95% CI, 0.0.77-1.62; P=0.57), cardiovascular mortality (RR, 1.00; 95% CI, 0.64-1.57; P=0.99), major adverse cardiovascular events (RR, 0.83; 95% CI, 0.63-1.10; P=20), target vessel revascularization (RR, 0.73; 95% CI, 0.48-1.11; P=0.14), myocardial infarction (RR, 0.74; 95% CI, 0.48-1.16; P=0.19), or stent thrombosis (RR, 1.06; 95% CI, 0.42-2.65; P=0.90). Conclusions In patients undergoing percutaneous coronary intervention for saphenous vein graft lesions, our results showed that there was no significant difference between DES and BMS for mortality, major adverse cardiovascular events, target vessel revascularization, myocardial infarction, or stent thrombosis.

Thirty-Day Readmission Rate and Costs After Percutaneous Coronary Intervention in the United States: A National Readmission Database Analysis.

BACKGROUND: The association of short-term readmissions after percutaneous coronary intervention (PCI) on healthcare costs has not been well studied. METHODS AND RESULTS: The Healthcare Cost and Utilization Project National Readmission Database encompassing 722 US hospitals was used to identify index PCI cases in patients ≥18 years old. Hierarchical regression analyses were used to examine the factors associated with risk of 30-day readmission and higher cumulative costs. We evaluated 206 869 hospitalized patients who survived to discharge after PCI from January through November 2013 and analyzed readmissions over 30 days after discharge. A total of 24 889 patients (12%) were readmitted within 30 days, with rates ranging from 6% to 17% across hospitals. Among the readmitted patients, 13% had PCI, 2% had coronary artery bypass surgery, and 3% died during the readmission. The most common reasons for readmission included nonspecific chest pain/angina (24%) and heart failure (11%). Mean cumulative costs were higher for those with readmissions ($39 634 versus $22 058; P<0.001). The multivariable analyses showed that readmission increased the log10 cumulative costs by 45% (ß: 0.445; P<0.001). There was no significant difference in cumulative costs by the type of insurance. CONCLUSIONS: In a national sample of inpatient PCI cases, 30-day readmissions were associated with a significant increase in cumulative costs. The majority of readmissions were because of low-risk chest pain that did not require any intervention. Ongoing effort is warranted to recognize and mitigate potentially preventable post-PCI readmissions.

The association of endothelial function and tone by digital arterial tonometry with MRI left ventricular mass in African Americans: the Jackson Heart Study.

Peripheral vascular endothelial dysfunction assessed by digital peripheral arterial tonometry (PAT) has been associated with risk for adverse cardiovascular events. We examined the relations of peripheral microvascular dysfunction and left ventricular mass in a community-based cohort of African Americans. We examined participants of the Jackson Heart Study who had PAT and cardiac magnetic resonance imaging evaluations between 2007 and 2013. Consistent with pertinent literature, left ventricular mass index (LVMI) was adjusted for body size by indexing to height2.7. Pearson's correlation and general linear regression analyses were used to relate reactive hyperemia index, baseline pulse amplitude (BPA), and augmentation index (markers of microvascular vasodilator function, baseline vascular pulsatility, and relative wave reflection, respectively) to LVMI after adjusting for traditional cardiovascular risk factors. A total of 440 participants (mean age 59 ± 10 years, 60% women) were included. Age- and sex-adjusted Pearson's correlation analysis suggested that natural log transformed LVMI was negatively correlated with reactive hyperemia index (coefficient: -0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P < .001). In multivariable analyses, higher loge LVMI was associated with higher BPA (ß: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes, hypertension, ratio of total cholesterol and high-density lipoprotein cholesterol, smoking, and history of cardiovascular disease. In a community-based sample of African Americans, higher baseline pulsatility measured by PAT was associated with higher LVMI by cardiac magnetic resonance imaging after adjusting for traditional risk factors.

Meta-analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease.

Despite the increase in use of percutaneous coronary intervention (PCI) in left main coronary disease, its efficacy compared with coronary artery bypass grafting (CABG) is unclear. We performed a meta-analysis of randomized controlled trials to assess the optimal revascularization strategy. Our search yielded 8 studies reporting relevant outcomes that were pooled using the inverse variance method, and the hazard ratio (HR) was calculated. The primary outcome was all-cause mortality, myocardial infarction (MI), or stroke (major adverse cardiac events [MACE]), and the secondary outcome was death/MI/stroke/repeat revascularization (expanded MACE). Differences in outcomes classified by follow-up duration (early: 0 to 1 year; late: 3 to 5 years) or anatomical complexity of coronary artery disease (SYNTAX score) were investigated. Our results suggest no difference in either early or late MACE (early: HR 0.81; 95% confidence interval [CI] 0.63 to 1.05; late: HR 1.12; 95% CI 0.80 to 1.56) or expanded MACE (early: HR 1.03; 95% CI 0.69 to 1.52; late: HR 1.16; 95% CI 0.95 to 1.43) between the 2 groups. There was an increased risk of expanded MACE with a high SYNTAX score for PCI (HR 1.47; 95% CI 1.13 to 1.92) at late follow-up. There were comparable rates of all-cause mortality and nonprocedural MI between the 2 groups with increased rates of repeat revascularization with PCI throughout the follow-up and higher rates of stroke with coronary artery bypass grafting early in the follow-up period. In conclusion, our analysis suggests that CABG may be preferable in patients with left main disease and high SYNTAX scores, assuming they are at low surgical risk, and PCI may be an acceptable alternative in patients with low-intermediate SYNTAX scores.

Impact of clinical and therapeutic factors on incident cardiovascular and cerebrovascular events in a population-based cohort of HIV-infected and non-HIV-infected adults.

BACKGROUND: Cardiovascular and cerebrovascular (CVD) events/diseases are a common cause of non-acquired immunodeficiency syndrome (AIDS)-related mortality in the aging human immunodeficiency virus (HIV)-infected population. The incidence rate and clinical correlates of CVD in people living with HIV/AIDS compared to the general population warrants further investigation. HYPOTHESIS: HIV/AIDS is associated with increased risk CVD compared to general population. METHODS: CVD events in a matched cohort of HIV-infected and non-HIV-infected adults, ≥18 years old, served through the South Carolina Medicaid program during 1994 to 2011 were examined using time-dependent proportional hazards regression and marginal structural modeling. RESULTS: A retrospective cohort of 13,632 adults was followed longitudinally for an average of 51 months. The adjusted hazard ratio (aHR) of incident CVD events was higher among HIV-infected individuals exposed to combination antiretroviral therapy (cART) (aHR = 1.15) compared to the non-HIV-infected group, but did not differ from the subgroup of cART-naïve HIV-infected adults. A higher aHR of incident CVD was associated with comorbid hypertension (aHR = 2.18), diabetes (aHR = 1.38), obesity (aHR = 1.30), tobacco use (aHR = 1.47), and hepatitis C coinfection (aHR = 1.32), and older age (aHR = 1.26), but with a lower risk among females (aHR = 0.86). A higher risk of incident CVD events was also apparent in HIV-infected individuals with exposure to both protease inhibitors (adjusted risk ratio [aRR] = 1.99) and non-nucleoside reverse transcriptase inhibitors (aRR = 2.19) compared to those with no exposure. Sustained viral load suppression was associated with a lower risk of incident CVD events (aRR = 0.74). CONCLUSIONS: After adjusting for traditional risk factors and sociodemographic differences, there is higher risk of incident cardiovascular events among HIV-infected individuals exposed to combined antiretroviral medications compared to the general population.

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea.

BACKGROUND: More evidence of the safety and effectiveness of hydroxyurea (HU) in community-based cohorts of pediatric patients with sickle cell disease (SCD) are needed. The association of HU with organ-specific clinical complications and adverse events is examined herein. METHODS: Medicaid medical and pharmacy claims for the calendar years January 1996 through December 2006 were used to identify a cohort of children and adolescent patients (ages 17 and under) with a diagnosis of SCD (homozygous) who were treated with HU and developed disparate complications or adverse side effects. Of the 2,194 pediatric SCD patients identified, 175 (8%) were treated with HU. Incidence density matching (1 case: 2 controls) was used to select the control group on age, gender, ethnicity, time in the Medicaid data set, and baseline severity resulting in a total study cohort of 523 cases. RESULTS: Organ-specific complications were more likely in the HU-treated group compared to non-HU-treated group: cardiovascular complications (odds ratio [OR] = 3.15; confidence interval [CI] = 1.97-5.03); hepatic complications (OR 5.41; CI = 3.54-8.27); renal complications (OR 5.09; CI 3.37-7.67); and pulmonary complications (OR 4.07; CI 1.88-8.79). Many of these conditions began developing before HU was prescribed. Developing three or more complications was also more likely in the HU group (27.4% vs. 7.0%, P < 0.0001). CONCLUSIONS: Extending previous findings to routine practice settings, HU is being administered to the most severely ill children with SCD, many of whom had already started to develop organ-specific complications, but it is not associated with development of serious adverse events.

Cost-effectiveness of adenotonsillectomy in reducing obstructive sleep apnea, cerebrovascular ischemia, vaso-occlusive pain, and ACS episodes in pediatric sickle cell disease.

In children with sickle cell disease (SCD), adenotonsillar hypertrophy or recurrent tonsillitis are frequently linked with an increased risk of obstructive sleep apnea, cerebrovascular ischemia, or frequent pain episodes and often require an adenoidectomy and/or tonsillectomy. Interventions designed to prevent these complications, control vaso-occlusive pain episodes, and avoid hospitalizations may reduce the significant personal and economic burden of SCD. This study compares episode recurrence and treatment costs for cerebrovascular ischemia, vaso-occlusive pain, acute chest syndrome (ACS), and obstructive sleep apnea in children who had an adenotonsillectomy (A/T surgery, N = 256; 11.7%) and a matched cohort of those who did not (N = 512; 23.3%) from a cohort of 2,194 children and adolescents with SCD from South Carolina's Medicaid system. A/T surgery was associated with a significantly reduced rate of visits over time for obstructive sleep apnea and cerebrovascular ischemia (e.g., stroke, transient ischemic attacks), but not with any change in the rate of visits for vaso-occlusive pain or ACS/pneumonia visits. The rate of mean acute (emergency and inpatient) service costs was significantly decreasing over time after an increase about the time the A/T surgery was performed. The cost-effectiveness of adenoidectomy and/or tonsillectomy for treating obstructive sleep apnea and preventing cerebrovascular ischemia without increasing vaso-occlusive pain episodes or long-term acute service costs in routine clinical practice settings was demonstrated. The matched control group of SCD patients without A/T surgery contained more patients with severe vaso-occlusive pain episodes, ACS visits, and higher mean total costs over time and appears to represent a different phenotype of children with SCD.